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Impacts of pI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

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neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： ramón pérez-núñez María Fernanda González Ana María Avalos Lisette Leyton Cellular Communication Laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced Center for Chronic Diseases(ACCDiS) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de Ciencias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(pI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the pI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/pI3K/AKT/connexin 43,and notch/pI3K/AKT pathways.While targeting the inactivation of the pI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the pI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(CD90)

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Factors associated with early virological response to peginterferon-α-2a/ribavirin in chronic hepatitis C

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World Journal of Gastroenterology 2013年第12期19卷 1943-1952页

作者： Javier García-Samaniego Miriam Romero Rafael Granados Remedios Alemán Miguel Jorge Juan Dolores Suárez ramón pérez Gregorio Castellano Carlos González-portela Liver Unit Hospital Carlos Ⅲ Centro de Investigación Biómedica en Red de Enfermedades Hepáticas y Digestivas Department of Gastroenterology Hospital Universitario de Gran Canaria Gastroenterology Service Hospital Universitario de Canarias Department of Gastroenterology Hospital Universitario Insular de Gran Canaria Internal Medicine Service Hospital Arquitecto Marcide Gastroenterology Service Hospital Central de Asturias Gastroenterology Service Hospital 12 de Octubre Gastroenterology Service Hospital Policlínico de Vigo

AIM: To evaluate the impact of sociodemographic/clinical factors on early virological response (EVR) to pegin-terferon/ribavirin for chronic hepatitis C (CHC) in clinical practice. METHODS: We conducted a multicenter, cross-sectional, observational study in Hepatology Units of 91 Spanish hospitals. CHC patients treated with peginterferon α-2a plus ribavirin were included. EVR was defined as undetectable hepatitis C virus (HCV)-ribonucleic acid (RnA) or ≥ 2 log HCV-RnA decrease after 12 wk of treatment. A bivariate analysis of sociodemographic and clinical variables associated with EVR was carried out. Independent factors associated with an EVR were analyzed using a multiple regression analysis that included the following baseline demographic and clinical variables: age (≤ 40 years vs > 40 years), gender, race, educational level, marital status and family status, weight, alcohol and tobacco consumption, source of HCV infection, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and gamma glutamyl transpeptidase (GGT) (≤ 85 IU/mL vs > 85 IU/mL), serum ferritin, serum HCV-RnA concentration (notype (1/4 vs 3/4), cirrhotic status and ribavirin dose (800/1000/1200 mg/d).RESULTS: A total of 1014 patients were included in the study. Mean age of the patients was 44.3 ± 9.8 years, 70% were male, and 97% were Caucasian. The main sources of HCV infection were intravenous drug abuse (25%) and blood transfusion (23%). Seventyeight percent were infected with HCV genotype 1/4 (68% had genotype 1) and 22% with genotypes 2/3. The HCV-RnA level was > 400 000 IU/mL in 74% of patients. The mean ALT and AST levels were 88.4 ± 69.7 IU/mL and 73.9 ± 64.4 IU/mL, respectively, and mean GGT level was 82 ± 91.6 IU/mL. The mean ferritin level was 266 ± 284.8 μg/L. Only 6.2% of patients presented with cirrhosis. All patients received 180 mg of peginterferon α-2a. The most frequently used ribavirin doses were 1000 mg/d (41%) and 1200 mg/d (41%). The planned treatment duration was 48 wk for 92

关键词： Antiviral therapy Baseline factors Early virological response peginterferon α-2a Ribavirin

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Acute cholestasis related to desloratidine

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World Journal of Gastroenterology 2005年第23期11卷 3647-3648页

作者： ramón pérez Luis Rodrigo Rosa pérez Ruth de Francisco Gastroenterology Service

TO THE EDITORDesloratidine (Clarinex, neoclarytin, Aerius, Azomyr, Opulis,Allex), the principal active metabolite of loratadine is itself a new oral antihistamine drug Its main indications are for the treatment of seasonal allergic rhinitis (SAR) and chronic idiopathic urticaria (CIU). The pharmacologic profile of desloratidine offers particular benefits, in terms of histamine H1-receptor binding potency and H1 selectivity. It has a half-life of 21-27 h, permitting a once-daily dose. no specific precautions are required with respect to its administration in renal or hepatic failure. no clinically relevant racial or gender variations in the disposition of desloratidine have been noted.We present here a clinical case of acute reversible idiosyncratic liver toxicity, related to its administration.

关键词：急性胆汁淤积抗组胺剂过敏性鼻炎慢性先天性风疹

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Solution of the Center problem for a Class of polynomial Differential Systems

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Acta Mathematica Sinica,English Series 2024年第7期40卷 1685-1696页

作者： Chang Jian Liu Jaume Llibre Rafael ramírez Valentín ramírez School of Mathematics(Zhuhai) Sun Yat-sen UniversityZhuhai519086P.R.China Departament de Matemàtiques Universitat Autònoma de Barcelona08193BellaterraBarcelonaCataloniaSpain Departament d’Enginyeria Informàtica i Matemàtiques Universitat Rovira i VirgiliAvinguda dels Paiïsos Catalans 2643007TarragonaCataloniaSpain

Consider the polynomial differential system of degree m of the form x=-y(1+μ(a_(2)x-a_(1)y))+x(v(a_(1)x+a_(2)y)+Ω_(m-1)(x,y)),y=x(1+μ(a_(2)x-a_(1)y))+y(v(a_(1)x+a_(2)y)+Ω_(m-1)(x,y)),whereμandνare real numbers such that(μ^(2)+v^(2))(μ+v(m-2))(a_(1)^(2)+a_(2)^(2))≠m>2 andΩ_(m−1)(x,y)is a homogenous polynomial of degree m−1.A conjecture,stated in J.Differential Equations 2019,suggests that whenν=1,this differential system has a weak center at the origin if and only if after a convenient linear change of variable(x,y)→(X,Y)the system is invariant under the transformation(X,Y,t)→(−X,Y,−t).For every degree m we prove the extension of this conjecture to any value ofνexcept for a finite set of values ofμ.

关键词： Center problem polynomial differential system

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From prediction to prevention:Machine learning revolutionizes hepatocellular carcinoma recurrence monitoring

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World Journal of Gastroenterology 2024年第7期30卷 631-635页

作者： Mariana Michelle ramírez-Mejía nahum Méndez-Sánchez plan of Combined Studies in Medicine Faculty of MedicineNational Autonomous University of MexicoDistrito Federal 04510Mexico Liver Research Unit Medica Sur Clinic&FoundationDistrito Federal 14050Mexico Faculty of Medicine National Autonomous University of MexicoDistrito Federal 04510Mexico

In this editorial,we comment on the article by Zhang et al entitled Development of a machine learning-based model for predicting the risk of early postoperative recurrence of hepatocellular carcinoma.Hepatocellular carcinoma(HCC),which is characterized by high incidence and mortality rates,remains a major global health challenge primarily due to the critical issue of postoperative recurrence.Early recurrence,defined as recurrence that occurs within 2 years posttreatment,is linked to the hidden spread of the primary tumor and significantly impacts patient survival.Traditional predictive factors,including both patient-and treatment-related factors,have limited predictive ability with respect to HCC recurrence.The integration of machine learning algorithms is fueled by the exponential growth of computational power and has revolutionized HCC research.The study by Zhang et al demonstrated the use of a groundbreaking preoperative prediction model for early postoperative HCC recurrence.Challenges persist,including sample size constraints,issues with handling data,and the need for further validation and interpretability.This study emphasizes the need for collaborative efforts,multicenter studies and comparative analyses to validate and refine the model.Overcoming these challenges and exploring innovative approaches,such as multi-omics integration,will enhance personalized oncology care.This study marks a significant stride toward precise,efficient,and personalized oncology practices,thus offering hope for improved patient outcomes in the field of HCC treatment.

关键词： Hepatocellular carcinoma Early recurrence Machine learning XGBoost model predictive precision medicine Clinical utility personalized interventions

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presynaptic endoplasmic reticulum architecture and hereditary spastic paraplegia

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neural Regeneration Research 2024年第3期19卷 485-486页

作者： Juan Josépérez-Moreno Instituto de Biomedicina de Sevilla(IBiS) Hospital Universitario Virgen Del Rocío/CSIC/Universidad de Sevillaand Departamento de Biología CelularFacultad de BiologíaUniversidad de SevillaSevilleSpain

Hereditary spastic paraplegia(HSp)is a clinically and genetically heterogeneous neurodegenerative disorder,characterized primarily by progressive spasticity and weakness in the lower limbs.pat ients can also experience peripheral neuropathy,cognitive impairment,and other neurological symptoms.To date,more than 80 genes have been implicated in HSp,encompassing various cellular components,although mutations in genes encoding endoplasmic reticulum(ER)-shaping proteins are the most prevalent(parodi et al.,2017).ER-shaping proteins are generally known for regulating the tubulation and curvation of the ER,but most of them show additional functions,including fusion of ER tubules,microtubule-severing,ER autophagy,lipid droplet synthesis,contact sites with other organelles(Öztürk et al.,2020).This highlights the complexity of studying the role of these proteins and the link between ER function and HSp.

关键词： reticulum endoplasmic

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Ca-based materials derived from calcined cigarette butts for CO_(2)capture and thermochemical energy storage

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Journal of Environmental Sciences 2024年第6期140卷 230-241页

作者： nabil Amghar Virginia Moreno pedro E.Sánchez-Jiménez Antonio perejón Luis A.pérez-Maqueda Instituto de Ciencia de Materiales de Sevilla C.S.I.C.-Universidad de SevillaC.Américo Vespucio4941092 SevillaSpain Instituto de Tecnología de Materiales(ITM) Universitat Politècnica de València(UPV)Plaza Ferrándiz y Carbonell 1AlcoyAlicante 03801Spain Departamento de Química Inorgánica Facultad de QuímicaUniversidad de Sevilla41012 SevillaSpain

Cigarette butts(CBs)are one of the most common types of litter in the world.Due to the toxic substances they contain,the waste generated poses a harmful risk to the environment,and therefore there is an urgent need for alternative solutions to landfill storage.Thus,this work presents a possible revalorization of this waste material,which implies interesting environmental benefits.CBs were used as sacrificial templates for the preparation of CaO-based materials by impregnation with calcium and magnesium nitrates followed by flaming combustion.These materials presented enhanced porosity for their use in the Calcium Looping process applied either to thermochemical energy storage or CO_(2)capture applications.The influence of the concentration of Ca and Mg in the impregnating solutions on the multicycle reactivity of the samples was studied.An improved multicycle performance was obtained in terms of conversion for both applications.

关键词： Cigarette butts Calcium-Looping CO_(2)Capture Thermochemical energy storage

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photosynthetic Gas Exchange and nitrogen Assimilation in Green Bean plants Supplied with Two Sources of Silicon

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phyton-International Journal of Experimental Botany 2024年第5期93卷 963-980页

作者： Julio C.Anchondo-páez Esteban Sánchez Carlos A.ramírez-Estrada Alondra Salcido-Martínez Erick H.Ochoa-Chaparro Department of plant physiology Centro de Investigación en Alimentación y DesarrolloCiudad Delicias33089México

Beans contain a wide range of vitamins,proteins,calcium,and zinc which make them an important food source for many countries.To meet the demand for bean production worldwide,large amounts of fertilizers and pesticides are used.However,the cost of production and environmental impact increases.To produce food sustainably,the use of beneficial nutrients such as silicon as a biostimulant has been proposed.However,information about the effect of different sources of silicon on the metabolism of bean plants is scarce.Bean plants cv.Strike were grown in pots for 60 days and the effect of foliar application of silicon nanoparticles and the silicon-based biostimulant Codasilat 4 concentrations(0,1,2,and 4 mM)on total biomass,yield,photosynthetic pigment concentration,photosynthetic activity,stomatal conductance,transpiration rate,chlorophyll fluorescence,and nitrogen assimilation were evaluated.The results obtained showed that the supply of silicon at a dose of 1 mM functioned as a biostimulant,favoring gas exchange and nitrogen assimilation within the plant,which stimulated growth and yield.The results of this research work allowed a better comprehension of the effects of silicon application through silicon nanoparticles and the biostimulant Codasilon the physiology of green bean plants.

关键词： nanoparticles silicon phaseolus vulgaris L.

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Influence of biomass burning on ozone levels in the Megalopolis of Central Mexico during the COVID-19 lockdown

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Journal of Environmental Sciences 2024年第9期143卷 99-115页

作者： Victor Almanza Luis Gerardo Ruiz-Suárez Ricardo Torres-Jardón Agustín García-Reynoso Iván Y.Hernández-paniagua Institute for Atmospheric Sciences and Climate Change National Autonomous University of MexicoCoyoacan 04510Mexico CityMexico

The massive reductions in anthropogenic emissions resulting from the COVID-19 lockdown provided a unique opportunity to evaluate the effect of mitigation measures aiming to abate air pollution.In Mexico,the total lockdown period took place during the dry-hot season when biomass burning activity is enhanced.Here,we investigate the role of biomass burning emissions on regional ozone levels in the Megalopolis of Central Mexico.The studied period covers the lockdown phases 2 and 3,and the first month of the new normal.We applied a factor separation technique and process analysis to estimate the pure and synergistic contributions of emission reductions under lockdown and that from biomass burning to daily ozone maximum concentrations in 7 metropolitan areas of different states in the Megalopolis.The results revealed that biomass burning plumes likely masked the effect of massive reductions from mobile emissions,impacted the pBL development during phase 3 and favored transition and mixed nO_(x)-limited and VOC-limited regional regimes.This contributed to increased ozone production in the middle to lower pBL by changing the regional background levels which potentially could bias high ozone production efficiency estimations.Given the Megalopolis contribution to economic and societal development at national scale,our study suggests that ozone mitigation measures during the dry-hot season targeting mainly mobile emissions will likely be offset by biomass burning plumes.A regional and synergic policy aiming to control biomass burning would help to reduce the occurrence of high ozone levels in Central Mexico with the co-benefit of tackling short-lived climate pollutants.

关键词： COVID-19 Mexico Megalopolis Ozone Factor Separation process Analysis

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From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

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neural Regeneration Research 2025年第3期20卷 660-670页

作者： Ernesto Doncel-pérez Gabriel Guízar-Sahagún Israel Grijalva-Otero Hospital nacional de parapléjicos de Toledo Servicio de Salud de Castilla La Mancha(SESCAM)ToledoSpain Medical Research Unit for neurological Diseases UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIIMSSCiudad de MéxicoMéxico

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.

关键词： neural regeneration neuroprotection spinal cord injury repair spinal cord injury treatments structural restoration of spinal cord injury

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